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. 2020 Aug;22(5):498-507.
doi: 10.1111/bdi.12876. Epub 2019 Dec 5.

Accelerated hippocampal biological aging in bipolar disorder

Gabriel R Fries  1   2   3 , Isabelle E Bauer  4 , Giselli Scaini  1 , Samira S Valvassori  5 , Consuelo Walss-Bass  1   3 , Jair C Soares  3   4 , Joao Quevedo  1   3   4   5
Affiliations

Accelerated hippocampal biological aging in bipolar disorder

Gabriel R Fries et al. Bipolar Disord. 2020 Aug.

Abstract

Objectives: Evidence suggests accelerated aging mechanisms in bipolar disorder (BD), including DNA methylation (DNAm) aging in blood. However, it is unknown whether such mechanisms are also evident in the brain, in particular in association with other biological clocks. To investigate this, we interrogated genome-wide DNAm in postmortem hippocampus from 32 BD-I patients and 32 non-psychiatric controls group-matched for age and sex from the NIMH Human Brain Collection Core.

Methods: DNAm age and epigenetic aging acceleration were estimated using the Horvath method. Telomere length (TL) and mitochondrial DNA (mtDNA) copy number were quantified by real-time PCR. Between-group differences were assessed by linear regression and univariate general linear models with age, sex, race, postmortem interval, tissue pH, smoking, and body mass index included as co-variates.

Results: Groups did not differ for epigenetic aging acceleration when considering the entire sample. However, after splitting the sample by the median age, an epigenetic aging acceleration was detected in patients compared to controls among older subjects (P = .042). While TL did not differ between groups, a reduction in mtDNA copy number was observed in patients compared to controls (P = .047). In addition, significant correlations were observed between epigenetic aging acceleration and TL (r = -.337, P = .006), as well as between TL and mtDNA copy number (r = .274, P = .028).

Conclusions: Hippocampal aging may underlie neurocognitive dysfunctions observed in BD patients. Moreover, our results suggest a complex cross-talk between biological clocks in hippocampus that may underlie clinical manifestations of premature aging in BD.

Keywords: DNA methylation; aging; bipolar disorder; epigenetic age; mitochondrial DNA copy number; telomere length.

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References

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